Gerrit Jan Hordijk

Qantitative dose-volume response analysis of changes in parotid gland function after radiotheraphy in the head-and-neck region

Abstract Purpose: To study the radiation tolerance of the parotid glands as a function of dose and volume irradiated. Methods and Materials: One hundred eight patients treated with primary or postoperative radiotherapy for various malignancies in the head-and-neck region were prospectively evaluated. Stimulated parotid flow rate was measured before radiotherapy and 6 weeks, 6 months, and 1 year after radiotherapy. Parotid gland dose-volume histograms were derived from CT-based treatment planning. The normal tissue complication probability model proposed by Lyman was fit to the data. A complication was defined as stimulated parotid flow rate Results: The mean stimulated preradiotherapy flow rate of 174 parotid glands was 0.34 mL/min. The mean flow rate reduced to 0.12 mL/min 6 weeks postradiotherapy, but recovered to a mean flow rate of 0.20 mL/min at 1 year after radiotherapy. Reduction in postradiotherapy flow rate correlated significantly with mean parotid dose. No threshold dose was found. Increasing the irradiated volume of parotid glands from 0%–40% to 90–100% in patients with a mean parotid dose of 35–45 Gy resulted in a decrease in flow ratio from, respectively, approximately 100% to less than 10% 6 weeks after radiation. The flow ratio of the 90%–100% group partially recovered to 15% at 6 months and to 30% at 1 year after radiotherapy. The normal tissue complication probability model parameter TD 50 (the dose to the whole organ leading to a complication probability of 50%) was found to be 31, 35, and 39 Gy at 6 weeks, 6 months, and 1 year postradiotherapy, respectively. The volume dependency parameter n was around 1, which means that the mean parotid dose correlates best with the observed complications. There was no steep dose-response curve ( m = 0.45 at 1 year postradiotherapy). Conclusions: This study on dose/volume/parotid gland function relationships revealed a linear correlation between postradiotherapy flow ratio and parotid gland dose and a strong volume dependency. No threshold dose was found. Recovery of parotid gland function was shown at 6 months and 1 year after radiotherapy. In radiation planning, attempts should be made to achieve a mean parotid gland dose at least below 39 Gy (leading to a complication probability of 50%).

Differences in coping style and locus of control between older and younger patients with head and neck cancer

Objectives:  This prospective study analyses whether older and younger patients with cancer of the head and neck make use of different coping styles and locus of control mechanisms, and how these mechanisms are related to quality of life (QOL) and depressive symptoms.

Quality of life in elderly patients with head and neck cancer one year after diagnosis

Little is known about quality of life (QOL) in elderly patients.

Survival analysis of head and neck squamous cell carcinoma: Influence of smoking and drinking

Head and neck squamous cell carcinomas (HNSCCs) are associated with tobacco and alcohol; however, the prognostic relevance of these substances is unclear.

Elderly patients with head and neck cancer: the influence of comorbidity on choice of therapy, complication rate, and survival.

Purpose of reviewComorbidity may be an important reason for head and neck surgeons to treat elderly patients less intensively. This article provides an overview of the influence of age and comorbidity on choice of therapy, postoperative complications, and survival. Recent findingsSeveral retrospective studies show that elderly patients can undergo surgery if they do not have severe comorbid disorders. Severe comorbidity influences the rate of postoperative complications, and the higher complication rate in older patients reported in some studies is probably due to a higher level of comorbidity. Comorbidity also affects the survival of cancer patients, but several studies have failed to detect a relation between age and survival after correction for comorbidity. Thus, although severe comorbidity may influence the choice of treatment, patient age as such should not be a reason to exclude patients from intensive therapy. SummaryIf severe comorbidity is not present, elderly patients should receive standard treatment for head and neck cancer. Treatment choice should be based on medical findings and patient preference, not on chronologic age.

Carcinoma of the larynx: the Dutch national guideline for diagnostics, treatment, supportive care and rehabilitation

PURPOSE This evidence based guideline aims to facilitate proper management and to prevent diverging views concerning diagnosis, treatment and follow-up of carcinoma of the larynx between the major referral centers for head and neck cancer in The Netherlands. METHOD A multidisciplinary committee was formed representing all medical and paramedical disciplines involved in the management of laryngeal cancer and all head and neck oncology centers in The Netherlands. This committee reviewed the literature and formulated statements and recommendations based on the level of evidence and consistency of the literature data. Where reliable literature data were not available, recommendations were based on expert opinion. RESULTS Strict criteria have been proposed for the radiological diagnostic procedures as well as for the pathology report. For carcinoma in situ and severe dysplasia, microsurgery, preferably by laser, is proposed. For all other stages of invasive carcinoma, a full course of radiotherapy as a voice conserving therapy is the treatment of choice. Only in cases with massive tumor volumes with invasion through the laryngeal skeleton, primary surgery is inevitable. For rehabilitation and supportive care, minimal criteria are described. Due to the complexity of therapy and relative rarity of larynx carcinoma, all patients should be seen at least once in a dedicated head and neck clinic. CONCLUSION This guideline for the management of larynx carcinoma was produced by a multidisciplinary national committee and based on scientific evidence wherever possible. This procedure of guideline development has created the optimal conditions for nationwide acceptance and implementation of the guideline.

Ki‐67 and p53 in T2 laryngeal cancer

Objective: To study the relationship between the proliferative capacity, represented by the immunohistochemical labeling index (LI) of proliferation marker Ki‐67, and the p53 status, as in theory an intact p53 cell cycle checkpoint system should result in a lower proliferative capacity. Study Design: From a group of 128 patients with a T2 laryngeal carcinoma, presented from 1989 to 1993 at the University Hospital Utrecht, 20 patients with recurrent disease and 16 patients without recurrent disease were randomly selected. All patients received primary irradiation. Methods: Denaturing gradient gel electrophoresis and immunohistochemistry determined the p53 status. MIB‐1 staining was used to determine the Ki‐67 LI. Results: In 36% of specimens we found a p53 mutation with overexpression (LI, 31%). In 8% a p53 mutation without p53 overexpression was found (LI, 18%). Forty‐two percent showed no mutation but, nevertheless, overexpression (LI, 35%). Neither mutation nor overexpression was found in 14% (LI, 38%). No correlation exists between p53 status and proliferative capacity of tumors (analysis of variance [ANOVA]; P = .104). The proliferation rate as established with Ki‐67 LI positively correlates with response to radiotherapy (P = .006). Conclusions: 1. Overexpression of wild‐type p53 protein does not result in cell cycle arrest measurable by a lower Ki‐67 LI in comparison with cases overexpressing mutant type p53 protein. 2. A high Ki‐67 LI correlates with a favorable response to radiotherapy. Laryngoscope, 108:1548–1552, 1998

The importance of vocal cord mobility in T2 laryngeal cancer.

In a retrospective study 75 patients with T2 laryngeal cancer treated from 1981 through 1985 were analysed. Of this group 71 patients had a full course of radiotherapy as primary therapy. All 71 patients were given 70 Gy/7 weeks on the primary and 50 Gy/5 weeks on the neck, 2 Gy per fraction. Various prognostic factors for local control and survival were studied. In our patient group we found vocal cord mobility to be an important prognostic factor for ultimate local control and survival. Patients with impaired cord mobility had a significantly worse ultimate local control (76%) than patients with normal cord mobility (98%) and a significantly worse corrected actuarial survival. It is concluded that impaired cord mobility means more advanced disease. Future studies will have to answer the question how to improve the local control rate in patients with impaired cord mobility, for example, by incorporating laryngectomy earlier in the treatment program of those patients who can not be cured by radiotherapy alone or by using innovative radiotherapy protocols.

Elderly patients with head and neck cancer: physical, social and psychological aspects after 1 year.

Objective Elderly patients with head and neck cancer often receive non-standard treatment for reasons other than comorbidity. In this prospective study we investigated how elderly patients fare 1 year after treatment in comparison with their younger counterparts. Material and Methods Seventy patients aged 45–60 years and 51 patients aged ≥70 years with cancer of the oral cavity, pharynx (stage II–IV) or larynx (stage III–IV) participated in the study before treatment and 1 year later. Each patient was interviewed and given a questionnaire concerning physical functioning, social contacts, depressive symptoms, satisfaction with treatment and future expectations. Results At 12 months, patients in both age groups reported significantly more depressive symptoms and less social support than before treatment, and their Karnofsky Performance Score was lower. However, there were no differences between elderly and younger patients. Approximately 90% of those in both age groups said that they would choose the same treatment again, and there was no age difference regarding the impact of treatment or expectations for the future. Conclusion This study shows that the impact of treatment on quality of life did not differ between elderly and younger patients with head and neck cancer. Therefore, standard treatment should be considered in elderly patients if no severe contraindications exist.

Radiotherapy in epithelial tumors of the parotid gland: Case presentation and literature review

A group of 113 patients irradiated for parotid tumor was studied retrospectively. Sixty-two patients were irradiated after superficial parotidectomy or enucleation of a pleomorphic adenoma. None of them had a recurrence after 5-15 years. Sixteen patients were irradiated postoperatively after surgery for a recurrence of pleomorphic adenoma. Only one of them had developed a recurrent tumor. Thirty-five patients with a malignant parotid tumor were treated by irradiation, 22 after surgery and 13 after biopsy only. Patients with a low malignancy tumor (10/11) and adenoid cystic carcinoma (6/12) responded better than patients with a high malignancy carcinoma (2/12). A tumor larger than 4 cm, facial nerve palsy, lymph node metastasis, and inoperability indicate a poor prognosis. With high dose radiotherapy it is possible to treat inoperable tumors successfully. Adenoid cystic carcinomas can respond well to irradiation alone.